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1.
J Psychosoc Nurs Ment Health Serv ; 62(7): 11-15, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38976856

RESUMO

The mental health needs of Asian American older adults are complex and multifaceted. Despite their rich diversity, Asian American older adults face significant challenges, including mental health stigma, cultural stress, limited English proficiency, and historical trauma. In addition, the coronavirus disease 2019 pandemic reignited preexisting anti-Asian attitudes of hostility, discrimination, blame, and scapegoating. The historical context of Asian immigration to the United States, impact of race-based discrimination, and recent resurgence of anti-Asian hate crimes impact mental health in Asian American older adults. Thus, there is a need for a culturally sensitive and competent mental health care workforce, culturally tailored interventions, and family involvement. In the context of research and policy, it is critical to prioritize increased funding and research focus on culturally tailored instrument development, interventions, and policy initiatives informed by recent findings to safeguard this population from hate crimes and discrimination. [Journal of Psychosocial Nursing and Mental Health Services, 62(7), 11-15.].


Assuntos
Asiático , COVID-19 , Estigma Social , Humanos , Asiático/psicologia , Asiático/estatística & dados numéricos , Idoso , Estados Unidos , COVID-19/etnologia , COVID-19/psicologia , Serviços de Saúde Mental , Saúde Mental , Racismo/psicologia , SARS-CoV-2 , Necessidades e Demandas de Serviços de Saúde
2.
Int Microbiol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977514

RESUMO

This study explored the extracellular metabolomic responses of three different Salmonella enterica serotype Typhimurium (S. Typhimurium) strains-ATCC 13311 (STy1), NCCP 16964 (STy4), and NCCP 16958 (STy8)-cultured at refrigeration temperatures. The objective was to identify the survival mechanisms of S. Typhimurium under cold stress by analyzing variations in their metabolomic profiles. Qualitative and quantitative assessments identified significant metabolite alterations on day 6, marking a critical inflection point. Key metabolites such as trehalose, proline, glycerol, and tryptophan were notably upregulated in response to cold stress. Through multivariate analyses, the strains were distinguished using three metabolites-4-aminobutyrate, ethanol, and uridine-as potential biomarkers, underscoring distinct metabolic responses to refrigeration. Specifically, STy1 exhibited unique adaptive capabilities through enhanced metabolism of betaine and 4-aminobutyrate. These findings highlight the variability in adaptive strategies among S. Typhimurium strains, suggesting that certain strains may possess more robust metabolic pathways for enhancing survival in refrigerated conditions.

3.
Nucleic Acids Res ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994567

RESUMO

Immune responses need to be regulated to prevent autoimmunity. CRISPR-Cas systems provide adaptive immunity in prokaryotes through the acquisition of short DNA sequences from invading viruses (bacteriophages), known as spacers. Spacers are inserted into the CRISPR locus and serve as templates for the transcription of guides used by RNA-guided nucleases to recognize complementary nucleic acids of the invaders and start the CRISPR immune response. In type II-A CRISPR systems, Cas9 uses the guide RNA to cleave target DNA sequences in the genome of infecting phages, and the tracrRNA to bind the promoter of cas genes and repress their transcription. We previously isolated a Cas9 mutant carrying the I473F substitution that increased the frequency of spacer acquisition by 2-3 orders of magnitude, leading to a fitness cost due to higher levels of autoimmunity. Here, we investigated the molecular basis underlying these findings. We found that the I473F mutation decreases the association of Cas9 to tracrRNA, limiting its repressor function, leading to high levels of expression of cas genes, which in turn increase the strength of the type II-A CRISPR-Cas immune response. We obtained similar results for a related type II-A system, and therefore our findings highlight the importance of the interaction between Cas9 and its tracrRNA cofactor in tuning the immune response to balanced levels that enable phage defense but avoid autoimmunity.

4.
Meat Sci ; 216: 109577, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38964227

RESUMO

This study aimed to evaluate the sous-vide cooking and ficin treatment effects on the tenderness of beef steak and optimize it for the elderly using response surface methodology (RSM). The M. semitendinosus (ST) from Chikso cattle was shaped into 5 × 5 × 2.54 cm pieces. Ficin solution was injected into the ST steak at 10% of the meat weight, and sous-vide cooked in a water bath at 65 °C for 6 or 12 h. As ficin concentration increased, L*- and a*-value, shear force, and hardness decreased, while soluble peptides increased (P < 0.05). As cooking time increased, cooking loss and collagen solubility of the steak increased (P < 0.05). An interaction effect between ficin and sous-vide cooking was found in L*- and a*-value, shear force, hardness, and soluble peptides (P < 0.05). A model to optimize the hardness for elderly people was established (R2 = 0.7991). Optimization conditions by RSM were 0.86 U/L with 8.87 h (23 N/cm3) for tooth intake (grade 1), 16.31 U/L with 13.24 h (3 N/cm3) for gums intake (grade 2), according to KS H 4897 and Universal Design Foods concept for the elderly. These optimized conditions enable the production of customized products tailored to the oral conditions of elderly people.

5.
J Colloid Interface Sci ; 675: 104-116, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38968631

RESUMO

Exploring precious metal-free bifunctional electrocatalysts for both the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) is essential for the practical application of rechargeable Zn-air battery (ZAB). Herein, Ni-doped Co9S8 nanoparticles embedded in a defect-rich N, S co-doped carbon matrix (d-NixCo9-xS8@NSC) are synthesized via a facile pyrolysis and acid treatment process. The introduction of abundant defects in both the carbon matrix and metal sulfide provides numerous active sites and significantly enhances the electrocatalytic performances for both the ORR and OER. d-NixCo9-xS8@NSC exhibits a superior half-wave potential of 0.841 V vs. RHE for the ORR and delivers a low overpotential of 0.329 V at 10 mA cm-2 for the OER. Additionally, Zn-air secondary battery using d-NixCo9-xS8@NSC as the air cathode displays a higher specific capacity of 734 mAh gZn-1 and a peak power density of 148.03 mW cm-2 compared to those of state-of-the-art Pt/C-RuO2 (673 mAh gZn-1 and 136.9 mW cm-2, respectively). These findings underscore the potential of d-NixCo9-xS8@NSC as a high-performance electrocatalyst for secondary ZABs, offering new perspectives on the design of efficient noble metal-free electrocatalysts for future energy storage and conversion applications.

6.
J Vet Sci ; 25(3): e40, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38834510

RESUMO

IMPORTANCE: The creation of robust maternal-embryonic interactions and implantation models is important for comprehending the early stages of embryonic development and reproductive disorders. Traditional two-dimensional (2D) cell culture systems often fail to accurately mimic the highly complex in vivo conditions. The employment of three-dimensional (3D) organoids has emerged as a promising strategy to overcome these limitations in recent years. The advancements in the field of organoid technology have opened new avenues for studying the physiology and diseases affecting female reproductive tract. OBSERVATIONS: This review summarizes the current strategies and advancements in the field of 3D organoids to establish maternal-embryonic interaction and implantation models for use in research and personalized medicine in assisted reproductive technology. The concepts of endometrial organoids, menstrual blood flow organoids, placental trophoblast organoids, stem cell-derived blastoids, and in vitro-generated embryo models are discussed in detail. We show the incorportaion of organoid systems and microfluidic technology to enhance tissue performance and precise management of the cellular surroundings. CONCLUSIONS AND RELEVANCE: This review provides insights into the future direction of modeling maternal-embryonic interaction research and its combination with other powerful technologies to interfere with this dialogue either by promoting or hindering it for improving fertility or methods for contraception, respectively. The merging of organoid systems with microfluidics facilitates the creation of sophisticated and functional organoid models, enhancing insights into organ development, disease mechanisms, and personalized medical investigations.


Assuntos
Organoides , Feminino , Animais , Gravidez , Humanos , Técnicas de Cultura de Células em Três Dimensões/métodos , Implantação do Embrião/fisiologia
7.
Appetite ; 200: 107555, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38878902

RESUMO

This study used mixed methods to explore the impact of front-of-package health claims and bonus pack messages on consumer evaluations. First, a comprehensive audit of cereal box packages at the world's largest retailer examined how these messages are presented in practice. It was found that negative claims are more frequent and positive claims are less frequent on products with a bonus pack message compared to those without. A subsequent experiment investigated how combinations of health claims and bonus pack messages influence consumer evaluations. It also found that health claims significantly influenced consumer preferences, while bonus pack messages diminished perceptions of food healthiness but increased perceived value. Pairing positive health claims with bonus pack messages, such as "Family Size," improved perceptions of healthiness. Moreover, positive health claims made products seem of lower value, whereas negative health claims did not affect perceived value. Health claims negatively affected value perceptions, even when paired with bonus pack messages like "Large Size." However, the negative effect of health claims on tastiness perceptions was mitigated with "Large Size". The study underscores the complexity of consumer decision-making, and offer insights for food marketers, emphasizing the need of a strategic approach in crafting health-related messaging and promotional strategies for product packaging.


Assuntos
Comportamento de Escolha , Comportamento do Consumidor , Rotulagem de Alimentos , Embalagem de Alimentos , Preferências Alimentares , Humanos , Feminino , Masculino , Adulto , Rotulagem de Alimentos/métodos , Preferências Alimentares/psicologia , Embalagem de Alimentos/métodos , Adulto Jovem , Pessoa de Meia-Idade , Promoção da Saúde/métodos , Percepção , Adolescente , Dieta Saudável/psicologia , Paladar
8.
Artigo em Inglês | MEDLINE | ID: mdl-38881387

RESUMO

OBJECTIVE: To identify the prevalence of and relevant information for video head impulse test (vHIT) abnormality in a large population. STUDY DESIGN: A cross-sectional design. SETTING: Korean National Health and Nutrition Examination Survey, 2021. METHODS: The sample was representative of the Korean population, with 2237 participants aged ≥40 years. A vHIT was performed to evaluate vestibular function. The vestibulo-ocular reflex (VOR) gain and the presence of reproducible catch-up saccades was assessed in a vHIT. Participants also completed questionnaires for demographics, socioeconomic status, and basic information regarding systemic diseases and dizziness and underwent hearing tests with automated pure-tone audiometry. RESULTS: The prevalence of vHIT abnormality was 22.5%, with unilateral (14.3%) being more common than bilateral (8.2%). The prevalence of vHIT abnormality increased significantly with age, with the highest rate observed in individuals aged >70 years (42.5%). Both hearing and VOR gain deteriorated with age, but the patterns of age-related progression were different. While hearing loss (HL) deteriorated gradually and progressively throughout adulthood, VOR gain deterioration was markedly evident after 70 years of age. CONCLUSION: Considering the high prevalence of vHIT abnormality, appropriate social and medical policies are needed to prevent associated injuries and improve patients' quality of life. The distinct age-related changes in HL and objective findings of vestibular dysfunction indicate the need for different approaches to address these social problems in aging countries.

9.
Biomimetics (Basel) ; 9(6)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38921209

RESUMO

We propose a genetic algorithm for optimizing oil skimmer assignments, introducing a tailored repair operation for constrained assignments. Methods essentially involve simulation-based evaluation to ensure adherence to South Korea's regulations. Results show that the optimized assignments, compared to current ones, reduced work time on average and led to a significant reduction in total skimmer capacity. Additionally, we present a deep neural network-based surrogate model, greatly enhancing efficiency compared to simulation-based optimization. Addressing inefficiencies in mobilizing locations that store oil skimmers, further optimization aimed to minimize mobilized locations and was validated through scenario-based simulations resembling actual situations. Based on major oil spills in South Korea, this strategy significantly reduced work time and required locations. These findings demonstrate the effectiveness of the proposed genetic algorithm and mobilized location minimization strategy in enhancing oil spill response operations.

10.
Invest Ophthalmol Vis Sci ; 65(5): 27, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38758638

RESUMO

Purpose: To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment epithelial (RPE) cellular mosaic and to visualize lifetime changes at different retinal eccentricities. Methods: NIR reflectance and autofluorescence were captured using a custom adaptive optics scanning light ophthalmoscope in 10 healthy subjects (23-64 years old) at seven eccentricities and in two eyes with retinal abnormalities. Repeatability was assessed across two visits up to 8 weeks apart. Endogenous retinal fluorophores and hydrophobic whole retinal extracts of Abca4-/- pigmented and albino mice were imaged to probe the fluorescence origin of NIR-AOFLIO. Results: The RPE mosaic was resolved at all locations in five of seven younger subjects (<35 years old). The mean lifetime across near-peripheral regions (8° and 12°) was longer compared to near-foveal regions (0° and 2°). Repeatability across two visits showed moderate to excellent correlation (intraclass correlation: 0.88 [τm], 0.75 [τ1], 0.65 [τ2], 0.98 [a1]). The mean lifetime across drusen-containing eyes was longer than in age-matched healthy eyes. Fluorescence was observed in only the extracts from pigmented Abca4-/- mouse. Conclusions: NIR-AOFLIO was repeatable and allowed visualization of the RPE cellular mosaic. An observed signal in only the pigmented mouse extract infers the fluorescence signal originates predominantly from melanin. Variations observed across the retina with intermediate age-related macular degeneration suggest NIR-AOFLIO may act as a functional measure of a biomarker for in vivo monitoring of early alterations in retinal health.


Assuntos
Oftalmoscopia , Imagem Óptica , Epitélio Pigmentado da Retina , Humanos , Epitélio Pigmentado da Retina/diagnóstico por imagem , Epitélio Pigmentado da Retina/metabolismo , Oftalmoscopia/métodos , Adulto , Pessoa de Meia-Idade , Animais , Feminino , Camundongos , Masculino , Adulto Jovem , Imagem Óptica/métodos , Reprodutibilidade dos Testes , Raios Infravermelhos , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Angiofluoresceinografia/métodos
11.
Int J Food Microbiol ; 419: 110738, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38772219

RESUMO

This study investigates the possibility of utilizing drip as a non-destructive method for assessing the freshness and spoilage of chicken meat. The quality parameters [pH, volatile base nitrogen (VBN), and total aerobic bacterial counts (TAB)] of chicken meat were evaluated over a 13-day storage period in vacuum packaging at 4 °C. Simultaneously, the metabolites in the chicken meat and its drip were measured by nuclear magnetic resonance. Correlation (Pearson's and Spearman's rank) and pathway analyses were conducted to select the metabolites for model training. Binary logistic regression (model 1 and model 2) and multiple linear regression models (model 3-1 and model 3-2) were trained using selected metabolites, and their performance was evaluated using receiver operating characteristic (ROC) curves. As a result, the chicken meat was spoiled after 7 days of storage, exceeding 20 mg/100 g VBN and 5.7 log CFU/g TAB. The correlation analysis identified one organic acid, eight free amino acids, and five nucleic acids as highly correlated with chicken meat and its drip during storage. Pathway analysis revealed tyrosine and purine metabolism as metabolic pathways highly correlated with spoilage. Based on these findings, specific metabolites were selected for model training: ATP, glutamine, hypoxanthine, IMP, tyrosine, and tyramine. To predict the freshness and spoilage of chicken meat, model 1, trained using tyramine, ATP, tyrosine, and IMP from chicken meat, achieved a 99.9 % accuracy and had an ROC value of 0.884 when validated using drip metabolites. This model 1 was improved by training with tyramine and IMP from both chicken meat and its drip (model 2), which increased the ROC value for drip metabolites from 0.884 to 0.997. Finally, selected two metabolites (tyramine and IMP) can predict TAB and VBN quantitatively through models 3-1 and 3-2, respectively. Therefore, the model developed using metabolic changes in drip demonstrated the capability to non-destructively predict the freshness and spoilage of chicken meat at 4 °C. To make generic predictions, it is necessary to expand the model's applicability to various conditions, such as different temperatures, and validate its performance across multiple chicken batches.


Assuntos
Galinhas , Embalagem de Alimentos , Carne , Animais , Carne/microbiologia , Carne/análise , Embalagem de Alimentos/métodos , Microbiologia de Alimentos , Armazenamento de Alimentos , Contagem de Colônia Microbiana , Vácuo , Contaminação de Alimentos/análise
12.
Food Sci Anim Resour ; 44(2): 443-463, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38764514

RESUMO

This study investigated the impact of activated carbon, palm activated carbon, and zeolite on horse oil (HO) extracted from horse neck fat using supercritical fluid extraction with deodorant-untreated HO (CON) as a comparison. The yield and lipid oxidation of deodorant untreated HO (CON) were not significantly affected by the three deodorants. However, deodorant-treated HOs exhibited significantly elevated levels of α-linolenic acid (C18:3n3) and eicosenoic acid (C20:1n9) compared to CON (p<0.05), while other fatty acids remained consistent. Zeolite-purified HO demonstrated significantly lower levels of volatile organic compounds (VOCs) than other treatments (p<0.05). Remarkably, zeolite decreased the concentration of pentane, 2,3-dimethyl (gasoline odor), by over 90%, from 177.17 A.U. ×106 in CON to 15.91 A.U. ×106. Zeolite also effectively eliminates sec-butylamine (ammonia and fishy odor) as compared to other deodorant-treated HOs (p<0.05). Additionally, zeolite reduced VOCs associated with the fruity citrus flavor, such as nonanal, octanal, and D-limonene in HO (p<0.05). This study suggests that integrating zeolite in supercritical fluid extraction enhances HO purification by effectively eliminating undesirable VOCs, presenting a valuable approach for producing high-quality HO production in the cosmetic and functional food industries.

13.
Nat Rev Clin Oncol ; 21(6): 407-427, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38589512

RESUMO

The treatment of patients with advanced-stage solid tumours typically involves a multimodality approach (including surgery, chemotherapy, radiotherapy, targeted therapy and/or immunotherapy), which is often ultimately ineffective. Nucleic acid-based drugs, either as monotherapies or in combination with standard-of-care therapies, are rapidly emerging as novel treatments capable of generating responses in otherwise refractory tumours. These therapies include those using viral vectors (also referred to as gene therapies), several of which have now been approved by regulatory agencies, and nanoparticles containing mRNAs and a range of other nucleotides. In this Review, we describe the development and clinical activity of viral and non-viral nucleic acid-based treatments, including their mechanisms of action, tolerability and available efficacy data from patients with solid tumours. We also describe the effects of the tumour microenvironment on drug delivery for both systemically administered and locally administered agents. Finally, we discuss important trends resulting from ongoing clinical trials and preclinical testing, and manufacturing and/or stability considerations that are expected to underpin the next generation of nucleic acid agents for patients with solid tumours.


Assuntos
Neoplasias , Ácidos Nucleicos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/terapia , Ácidos Nucleicos/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Terapia Genética/métodos , Nanopartículas/uso terapêutico , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos
14.
Gland Surg ; 13(3): 340-350, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38601290

RESUMO

Background: The changing medical education environment emphasizes the need for time efficiency, increasing the demand for competency-based medical education to improve trainees' learning strategies. This study was performed to determine the competencies required for successful performance of robotic thyroidectomy (RT) and to determine the consensus of experts for performance of RT. Methods: Data were collected through 12 semi-structured interviews with RT experts and 11 field observations. Cognitive task analysis was performed to determine the competencies required for experts to perform RT. A modified Delphi methodology was used to determine how 20 experts rated the importance of each item of RT performance on a Likert 7-point scale. The criteria for the Delphi consensus were set at a Cronbach's α≥0.80 with two survey rounds. Results: After 11 field observations and 12 semi-structured interviews, 89 items were identified within six modules. These items were grouped into sub-modules according to their theme. The modified Delphi survey, involving 21 experts, reached the consensus standard during the second round (Cronbach's α=0.954), enabling the identification of the 64 most important items within six modules related to RT performance: midline incision to isthmectomy (MID module; n=8), lateral dissection (LAT module; n=7), preservation of inferior parathyroid glands (INF module; n=16), preservation of recurrent laryngeal nerve and dissection of the ligament of Berry (BER module; n=21), dissection of the thyroid upper pole (SUP module; n=10), and specimen removal and closure (END module; n=2). Conclusions: This mixed-method study combining qualitative and quantitative methodology identified modules of core competencies required to perform RT. These modules can be used as a standard and objective guide to train surgeons to perform RT and evaluate outcomes.

15.
J Colloid Interface Sci ; 665: 922-933, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38569309

RESUMO

Utilizing renewable electricity for water electrolysis offers a promising way for generating high-purity hydrogen gases while mitigating the emission of environmental pollutants. To realize the water electrolysis, it is necessary to develop highly active and precious metal-free electrocatalyst for oxygen evolution reaction (OER) which incurs significant overpotential due to its complicated four-electron transfer mechanism. Hence, we propose a facile preparation method for hollow-structured Fe and F dual-doped CoS2 nanosphere (Fe-CoS2-F) as an efficient OER electrocatalyst. The uniform hollow and porous structure of Fe-CoS2-F enlarge the specific surface area and increase the number of exposed active sites. Furthermore, the Fe and F dual-dopants synergistically contributed to the adjustment of electronic structure, thereby promoting the adsorption/desorption of oxygen-containing reaction intermediates on active sites during the alkaline OER procedure. As a result, the prepared Fe-CoS2-F exhibits outstanding OER activity, characterized by a low overpotential of 298 mV to achieve a current density of 10 mA cm-2 and a Tafel slope as small as 46.0 mV dec-1. Based on computational theoretical calculations, the introduction of the dual-dopants into CoS2 structure reduce the excessively strong adsorption energy of reaction intermediate in the rate determining step, leading to effectively promoted electrocatalytic cycle for OER in alkaline environment. This study presents an effective strategy for preparing noble metal-free OER electrocatalysts with promising potential for large-scale industrial water electrolysis.

16.
Food Funct ; 15(8): 4564-4574, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38584588

RESUMO

This study aimed to investigate the potential of beef peptides (BPs) in mitigating muscle atrophy induced by dexamethasone (DEX) with underlying three mechanisms in vitro (protein degradation, protein synthesis, and the oxidative stress pathway). Finally, the anti-atrophic effect of BPs was enhanced through purification and isolation. BPs were generated using beef loin hydrolyzed with alcalase/ProteAX/trypsin, each at a concentration of 0.67%, followed by ultrafiltration through a 3 kDa cut-off. BPs (10-100 µg mL-1) dose-dependently counteracted the DEX-induced reductions in myotube diameters, differentiation, fusion, and maturation indices (p < 0.05). Additionally, BPs significantly reduced FoxO1 protein dephosphorylation, thereby suppressing muscle-specific E3 ubiquitin ligases such as muscle RING-finger containing protein-1 and muscle atrophy F-box protein in C2C12 myotubes at concentrations exceeding 25 µg mL-1 (p < 0.05). BPs also enhanced the phosphorylation of protein synthesis markers, including mTOR, 4E-BP1, and p70S6K1, in a dose-dependent manner (p < 0.05) and increased the mRNA expression of antioxidant enzymes. Fractionated peptides derived from BPs, through size exclusion and polarity-based fractionation, also demonstrated enhanced anti-atrophic effects compared to BPs. These peptides downregulated the mRNA expression of primary muscle atrophy markers while upregulated that of antioxidant enzymes. Specifically, peptides GAGAAGAPAGGA (MW 924.5) and AFRSSTKK (MW 826.4) were identified from fractionated peptides of BPs. These findings suggest that BPs, specifically the peptide fractions GAGAAGAPAGGA and AFRSSTKK, could be a potential strategy to mitigate glucocorticoid-induced skeletal muscle atrophy by reducing the E3 ubiquitin ligase activity.


Assuntos
Fibras Musculares Esqueléticas , Atrofia Muscular , Estresse Oxidativo , Peptídeos , Animais , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Bovinos , Proteólise/efeitos dos fármacos , Linhagem Celular , Biossíntese de Proteínas/efeitos dos fármacos , Carne Vermelha , Proteínas Musculares/metabolismo , Dexametasona/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fosforilação , Serina-Treonina Quinases TOR/metabolismo
17.
Pharmaceuticals (Basel) ; 17(4)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38675489

RESUMO

No standardized in vitro cell culture models for glioblastoma (GBM) have yet been established, excluding the traditional two-dimensional culture. GBM tumorspheres (TSs) have been highlighted as a good model platform for testing drug effects and characterizing specific features of GBM, but a detailed evaluation of their suitability and comparative performance is lacking. Here, we isolated GBM TSs and extracellular matrices (ECM) from tissues obtained from newly diagnosed IDH1 wild-type GBM patients and cultured GBM TSs on five different culture platforms: (1) ordinary TS culture liquid media (LM), (2) collagen-based three-dimensional (3D) matrix, (3) patient typical ECM-based 3D matrix, (4) patient tumor ECM-based 3D matrix, and (5) mouse brain. For evaluation, we obtained transcriptome data from all cultured GBM TSs using microarrays. The LM platform exhibited the most similar transcriptional program to paired tissues based on GBM genes, stemness- and invasiveness-related genes, transcription factor activity, and canonical signaling pathways. GBM TSs can be cultured via an easy-to-handle and cost- and time-efficient LM platform while preserving the transcriptional program of the originating tissues without supplementing the ECM or embedding it into the mouse brain. In addition to applications in basic cancer research, GBM TSs cultured in LM may also serve as patient avatars in drug screening and pre-clinical evaluation of targeted therapy and as standardized and clinically relevant models for precision medicine.

19.
Science ; 384(6694): 458-465, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38662818

RESUMO

Based on an extensive model intercomparison, we assessed trends in biodiversity and ecosystem services from historical reconstructions and future scenarios of land-use and climate change. During the 20th century, biodiversity declined globally by 2 to 11%, as estimated by a range of indicators. Provisioning ecosystem services increased several fold, and regulating services decreased moderately. Going forward, policies toward sustainability have the potential to slow biodiversity loss resulting from land-use change and the demand for provisioning services while reducing or reversing declines in regulating services. However, negative impacts on biodiversity due to climate change appear poised to increase, particularly in the higher-emissions scenarios. Our assessment identifies remaining modeling uncertainties but also robustly shows that renewed policy efforts are needed to meet the goals of the Convention on Biological Diversity.


Assuntos
Biodiversidade , Mudança Climática , Extinção Biológica
20.
J Med Chem ; 67(7): 5699-5720, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38530425

RESUMO

We report herein the potential of colony-stimulating factor-1 receptor (CSF1R) inhibitors as therapeutic agents in neuroinflammatory diseases, with a focus on Alzheimer's disease (AD). Employing a carefully modified scaffold, N-(4-heterocycloalkyl-2-cycloalkylphenyl)-5-methylisoxazole-3-carboxamide, we identify highly selective and potent CSF1R inhibitors─7dri and 7dsi. Molecular docking studies shed light on the binding modes of these key compounds within the CSF1R binding site. Remarkably, kinome-wide selectivity assessment underscores the impressive specificity of 7dri for CSF-1R. Notably, 7dri emerges as a potent CSF-1R inhibitor with favorable cellular activity and minimal cytotoxicity among the synthesized compounds. Demonstrating efficacy in inhibiting CSF1R phosphorylation in microglial cells and successfully mitigating neuroinflammation in an in vivo LPS-induced model, 7dri establishes itself as a promising antineuroinflammatory agent.


Assuntos
Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Fator Estimulador de Colônias de Macrófagos , Fosforilação , Simulação de Acoplamento Molecular , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos , Receptores Proteína Tirosina Quinases/metabolismo
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